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Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease
Open accessAbstract
The WGATAR motif is a common nucleotide sequence found in the transcriptional regulatory regions of numerous genes. In vertebrates, these motifs are bound by one of six factors (GATA1 to GATA6) that constitute the GATA family of transcriptional regulatory proteins. Although originally considered for their roles in hematopoietic cells and the heart, GATA factors are now known to be expressed in a wide variety of tissues where they act as critical regulators of cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and especially the gonads. Insights into the functional roles played by GATA factors in adult organ systems have been hampered by the early embryonic lethality associated with the different Gata-null mice. This is now being overcome with the generation of tissue-specific knockout models and other knockdown strategies. These approaches, together with the increasing number of human GATA-related pathologies have greatly broadened the scope of GATA-dependent genes and, importantly, have shown that GATA action is not necessarily limited to early development. This has been particularly evident in endocrine organs where GATA factors appear to contribute to the transcription of multiple hormone-encoding genes. This review provides an overview of the GATA family of transcription factors as they relate to endocrine function and disease.
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“GATA4 is a zinc finger transcription factor essential for the development of various organs, including heart, testis, foregut, liver, and ventral pancreas (37).”
From The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. (2015) · cites this paper as [37]
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“The gonads also express several GATA factors that are known to regulate steroidogenic gene expression [reviewed in (37)].”
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“Beside steroid receptors, several other transcription factors such as FOS [27], GATA1 [32] and ETS1 [10], known to participate in critical normal developmental steps or to events underlying tumorigenesis, directly interact with SRAP (Table 1).”
BackgroundGATA4 Is a Critical Regulator of Gonadectomy-Induced Adrenocortical Tumorigenesis in Mice
Krachulec, J., Vetter, M., Schrade, A., Löbs, A., Bielińska, M., Cochran, R. S., Kyrönlahti, A., Pihlajoki, M., Parviainen, H., Jay, P. Y., et al. (2012) · Endocrinology · doi:10.1210/en.2011-2135 · Cited by 25
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“Transcription of several other Leydig cell-expressed genes have been proposed to be targeted by either GATA4 and/or GATA6 [reviewed in (4, 18)].”
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“transcriptional partners in testis cells (59), makes this an unlikely possibility.”
BackgroundSelf-citationGATA factors in endocrine neoplasia
Pihlajoki, M., Färkkilä, A., Soini, T., Heikinheimo, M., & Wilson, D. B. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.027 · Cited by 25
“In the adult ovary, GATA4 is present in theca cells and in granulosa cells of primary, preantral, and antral follicles, but not in primordial follicles or luteal cells (LaVoie et al., 2004; Viger et al., 2008).”
BackgroundInfluentialSelf-citationRole of the pioneer transcription factor GATA2 in health and disease
Aktar, A., & Heit, B. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02359-8 · Cited by 23
Sayasith, K., Sirois, J., & Lussier, J. G. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.111849 · Cited by 23
“In ovarian follicles, COUP-TFI, COUP-TFII, and GATA4 proteins are expressed in granulosa and thecal cells [47–54] and are known to be involved in the regulation of genes related to follicle growth and steroid synthesis, including CYP19, FSHR, StAR, and LHb-subunit [50, 55–58].”
BackgroundMolecular characterization and expression profiles of GATA6 in tongue sole (Cynoglossus semilaevis)
Liu, J., Zhang, W., Sun, Y., Wang, Z., Zhang, Q., & Wang, X. (2016) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2016.03.006 · Cited by 23
“The N-terminal zinc finger contributes to the specificity and stability of the DNA-binding, and the C-terminal zinc finger is required for interacting with the DNA sequence element WGATAR or related DNA cis-elements (Lowry and Atchley, 2000; Patient and McGhee, 2002; Viger et al., 2008).”
BackgroundGATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3
Pei, Y., Yao, Q., Yuan, S., Xie, B., Liu, Y., Ye, C., & Zhuo, H. (2016) · Oncotarget · doi:10.18632/oncotarget.12839 · Cited by 23
“GATA4, 5, and 6 are predominantly expressed in organs originating from mesoderm or endoderm, such as the liver, lungs, heart, and gut [13], and GATA4 specifically contributes to mammalian liver development [14].”
BackgroundRegulation of Follicle Formation and Development by Ovarian Signaling Pathways
Prasasya, R. D., & Mayo, K. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813209-8.00002-9 · Cited by 23
Transcription Factor GATA‐4 Is Abundantly Expressed in Childhood but Not in Adult Liver Tumors
Soini, T., Haveri, H., Elo, J. M., Kauppinen, M., Kyrönlahti, A., Salo, M. K., Lohi, J., Andersson, L. C., Wilson, D. B., & Heikinheimo, M. (2011) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31822d52cf · Cited by 22
“Moreover, GATA-4 (18) and Epo, its putative target gene in the fetal liver (14,19–22), have been connected to tumorigenesis of many human organs.”
BackgroundSelf-citationGATA Regulation and Function During the Ovarian Life Cycle
Bennett‐Toomey, J., & Stocco, C. O. (2018) · Vitamins and hormones · doi:10.1016/bs.vh.2018.01.014 · Cited by 22
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Self-citationExpression of wnt4/5 during reproductive cycle of catfish and wnt5 promoter analysis
Prathibha, Y., & Senthilkumaran, B. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0104 · Cited by 22
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“Among the members of the evolutionally conserved GATA transcription factor family [79], GATA3 is known for its critical role in regulating luminal cell fate in the mammary gland [60, 61].”
BackgroundGenetic Control of Ovarian Development
Tevosian, S. G. (2012) · Sexual Development · doi:10.1159/000339511 · Cited by 22
“Genetic Regulators of Ovarian Development Gata4/6 and Fog2 The transcription factors of the GATA family (GATA binding proteins 4 and 6) and their co-factor FOG2 ( Zfpm2 , zinc finger protein, multitype 2) have been implicated as key drivers of multiple developmental processes [Molkentin, 2000; Patient and McGhee, 2002…”
BackgroundThe effect of human GATA4 gene mutations on the activity of target gonadal promoters
Bouchard, M. F., Taniguchi, H., & Viger, R. S. (2008) · Journal of Molecular Endocrinology · doi:10.1677/jme-08-0089 · Cited by 22
“In the reproductive tract, GATA4 is prominently expressed in somatic cells of both the testis and ovary, where it has been shown and/or proposed to regulate the transcription of numerous target genes (Viger et al. 2008).”
BackgroundInfluentialSelf-citationPangas, S. A., & Rajkovic, A. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00021-1 · Cited by 22
Wen, L., Yuan, Q., Sun, M., Niu, M., Wang, H., Fu, H., Zhou, F., Yao, C., Wang, X., Li, Z., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.14985 · Cited by 21
“RTPCR revealed that the transcripts of AR, BMP4, BMP6, GATA4, GDNF, SCF, SOX9 and WT1 were expressed in the immortalized human cells (Figure 2A), which was comparable to the expression level of these genes in primary human Sertoli cells (Figure 2B).”
BackgroundInfluentialTranscriptional control of human gametogenesis
Fang, F., Iaquinta, P. J., Xia, N., Liu, L., Diao, L., & Pera, R. A. R. (2022) · Human Reproduction Update · doi:10.1093/humupd/dmac002 · Cited by 23
“GATA4, a zinc finger transcription factor, also cooperatively interacts with NR5A1 to regulate downstream genes critical for testis differentiation (Viger et al., 2008).”
GATA transcription factors in vertebrates: evolutionary, structural and functional interplay
Tang, Y., Wei, Y., He, W., Wang, Y., Zhong, J., & Qin, C. (2013) · Molecular Genetics and Genomics · doi:10.1007/s00438-013-0802-4 · Cited by 21
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Hilbold, E. A., Distl, O., Hoedemaker, M., Wilkening, S., Behr, R., Rajkovic, A., Langeheine, M., Rode, K., Jung, K., Metzger, J., et al. (2020) · Cells · doi:10.3390/cells9030676 · Cited by 21
“SCs express GATA4 from the onset of their differentiation through to adulthood (reviewed in [124]).”
BackgroundRudzinskas, S. A., Goff, A. C., Mazzu, M. A., Schiller, C. E., Meltzer-Brody, S. E., Rubinow, D. R., Schmidt, P. J., & Goldman, D. A. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01985-5 · Cited by 20
GATA4 negatively regulates osteoblast differentiation by downregulation of Runx2
Song, I., Kim, K., Kim, J. H., Lee, Y., Jung, H.-J., Byun, H., Yoon, G., & Kim, N. (2014) · BMB Reports · doi:10.5483/bmbrep.2014.47.8.225 · Cited by 20
“Because GATA family members share a highly conserved DNA-binding domain, there is apparent redundancy in DNA-binding properties to target GATA sequences (15).”
BackgroundQi, J., Huo, L., Zhu, Y. T., & Zhu, Y.-J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.579839 · Cited by 20
“GATA3 is a member of the GATA transcription factor family (51, 52).”
BackgroundJahromi, M. S., Tehrani, F. R., Noroozzadeh, M., Zarkesh, M., Ghasemi, A., & Zadeh–Vakili, A. (2016) · Gene · doi:10.1016/j.gene.2016.07.067 · Cited by 20
An, L., Zhang, M., Lin, Y., Jiang, T., Xu, K., Xiao, S., Cai, L., Kwan, H. Y., Liu, Z., & Su, T. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154199 · Cited by 19
Bhardwaj, A., Song, H.-W., Beildeck, M. E., Kerkhofs, S., Castoro, R. J., Shanker, S., Gendt, K. D., Suzuki, K., Claessens, F., Issa, J. J., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2011-1059 · Cited by 19
“Furthermore, GATA factors are required for a wide range of functions (37), and thus their knockdown could have widespread pleiotropic effects that are difficult to interpret.”
BackgroundNotch signalling regulates steroidogenesis in mouse ovarian granulosa cells
Wang, Y., Lu, E., Bao, R., Xu, P., Feng, F., Wen, W., Dong, Q., Hu, C., Li, X., Tang, M., et al. (2019) · Reproduction Fertility and Development · doi:10.1071/rd18281 · Cited by 19
Yuan, C., Zhang, C., Qi, Y., Li, D., Hu, Y., & Huang, D. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.110042 · Cited by 19
Generation of cell-permeant recombinant human transcription factor GATA4 from E. coli
Haridhasapavalan, K. K., Sundaravadivelu, P. K., Bhattacharyya, S., Ranjan, S. H., Raina, K., & Thummer, R. P. (2021) · Bioprocess and Biosystems Engineering · doi:10.1007/s00449-021-02516-8 · Cited by 18
“In addition, it is also crucial for the induction of definitive endoderm, and therefore essential for the formation of endodermal lineages [3].”
BackgroundDeLaForest, A., Kohlnhofer, B. M., Franklin, O. D., Stavniichuk, R., Thompson, C. A., Pulakanti, K., Rao, S., & Battle, M. A. (2021) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2021.05.021 · Cited by 18
Röhrig, T., Pihlajoki, M., Ziegler, R., Cochran, R. S., Schrade, A., Schillebeeckx, M., Mitra, R. D., Heikinheimo, M., & Wilson, D. B. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.12.003 · Cited by 18
Self-citationSTARD6 is expressed in steroidogenic cells of the ovary and can enhance de novo steroidogenesis
LaVoie, H. A., Whitfield, N. E., Shi, B., King, S. R., Bose, H. S., & Hui, Y. Y. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370213517616 · Cited by 19
“manner.(18,19) Combined GATA4 þ GATA6 reduction significantly lowered STARD6 mRNA levels, indicating that STARD6 is either a direct GATA target gene like STARD1, or regulated by a signal dependent on these transcription factors.”
BackgroundLiu, J., Zhang, W., Du, X., Jiang, J., Wang, C., Wang, X., Zhang, Q., & He, Y. (2015) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpb.2015.12.001 · Cited by 18
“GATA4 typically interacts with cofactors, including SF-1, FOG2, and LRH-1, to regulate target genes (Viger et al., 2008).”
BackgroundAGata4nuclear GFP transcriptional reporter to study endoderm and cardiac development in the mouse
Simon, C. S., Zhang, L., Wu, T., Cai, W., Saiz, N., Nowotschin, S., Cai, C., & Hadjantonakis, A. (2018) · Biology Open · doi:10.1242/bio.036517 · Cited by 18
GATA transcription factors in testicular adrenal rest tumours
Engels, M., Span, P. N., Mitchell, R. T., Heuvel, J. J. T. M., Zanten, M. M. V., van Herwaarden, A. E., de Kaa, C. A. H., Oosterwijk, E., Stikkelbroeck, N. M. M. L., Smith, L. B., et al. (2017) · Endocrine Connections · doi:10.1530/ec-17-0215 · Cited by 17
Soini, T., Pihlajoki, M., Andersson, N., Lohi, J., Huppert, K. A., Rudnick, D. A., Huppert, S. S., Wilson, D. B., Pakarinen, M. P., & Heikinheimo, M. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00362.2017 · Cited by 17
Self-citationFouquet, B., Santulli, P., Noël, J., & Misrahi, M. (2016) · BBA Clinical · doi:10.1016/j.bbacli.2016.11.002 · Cited by 17
GATA4 Autoregulates Its Own Expression in Mouse Gonadal Cells via Its Distal 1b Promoter1
Mazaud‐Guittot, S., Prud’homme, B., Bouchard, M. F., Bergeron, F., Daems, C., Tevosian, S. G., & Viger, R. S. (2013) · Biology of Reproduction · doi:10.1095/biolreprod.113.113290 · Cited by 16
“In the gonads, the Sry, Sox9, and Dmrt1 genes are important early targets [14-16], while later in life, the regulation of steroidogenic genes appears to be an important function for GATA4 [6, 17-23].”
BackgroundSelf-citationHui, Y. Y., & LaVoie, H. A. (2008) · Endocrinology · doi:10.1210/en.2008-0484 · Cited by 16
The Battle of the Sexes: Human Sex Development and Its Disorders
Biason‐Lauber, A. (2016) · Results and problems in cell differentiation · doi:10.1007/978-3-319-31973-5_13 · Cited by 16
Variants in cardiac GATA genes associated with bicuspid aortic valve
Alonso‐Montes, C., Martı́n, M., Martínez‐Arias, L., Coto, E., Naves‐Díaz, M., Morı́s, C., Cannata-Andía, J. B., & Rodrı́guez, I. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.13027 · Cited by 15
“In vertebrates, this family consists of six members divided in two subgroups based on their sequence homology and tissue location: GATA1, 2, and 3 are mainly implicated in hematopoietic development and GATA4, 5, and 6 are essential in cardiovascular embryogenesis, as well as in other tissues derived from mesoderm and…”
BackgroundTokumoto, M., Lee, J., Fujiwara, Y., & Satoh, M. (2014) · The Journal of Toxicological Sciences · doi:10.2131/jts.39.735 · Cited by 16
“There are multiple GATA family transcription factors (GATA1– GATA6) for the binding GATA element in vertebrates (Viger et al., 2008).”
BackgroundZinc Finger Protein, Multitype 1, Suppresses Human Th2 Development via Downregulation of IL-4
Kitamura, N., Mori, A., Tatsumi, H., Nemoto, S., Hiroi, T., & Kaminuma, O. (2011) · International Archives of Allergy and Immunology · doi:10.1159/000327292 · Cited by 15
“The GATA family transcription factors interact with (A/T)GATA(A/G) motifs in the promoter/enhancer and regulatory regions of numerous genes via 2 highly conserved zinc fingers [”
BackgroundAn Ebox Element in the Proximal Gata4 Promoter Is Required for Gata4 Expression In Vivo
Sab, A. B., Bouchard, M., Béland, M., Prud’homme, B., Souchkova, O., Viger, R. S., & Pilon, N. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029038 · Cited by 15
“5 [5,6,7].”
Self-citationZheng, Y., Sun, Y., Yang, Y., Zhang, S., Xu, T., Xin, W., Wu, S.-L., & Zhang, X. (2019) · Molecular Pain · doi:10.1177/1744806919863292 · Cited by 15
“The GATA family of transcription factor is composed of six members including GATA1–6 and was originally considered for their roles in hematopoietic cells.(5) (1)Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital,”
BackgroundA New Pathway for Senescence Regulation
Cao, X., & Li, M. (2015) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2015.11.002 · Cited by 16
“GATA4 is well recognized for its involvement in the regulation of embryonic development of heart, testis, ovary, ventral pancreas [12,13].”
BackgroundLi, J., Chen, W., Wang, D., Zhou, L., Sakai, F., Guan, G., & Nagahama, Y. (2011) · Journal of Reproduction and Development · doi:10.1262/jrd.11-131s · Cited by 14
“GATA4 interacts with several proteins, including its cofactors FOG2, SF-1/ NR5A1 and LRH-1/NR5A2 [7].”
BackgroundResultInfluentialKLF6 cooperates with NUR77 and SF1 to activate the human INSL3 promoter in mouse MA-10 leydig cells
Tremblay, M. A., Mendoza-Villarroel, R. E., Robert, N. M., Bergeron, F., & Tremblay, J. (2016) · Journal of Molecular Endocrinology · doi:10.1530/jme-15-0139 · Cited by 14
“…factors known to be present in both Sertoli and Leydig cells include the MADS-box factors MEF2 (Daems et al. 2014), the zinc finger factor GATA4 (reviewed in Viger et al. 2008) and the nuclear receptors SF1 (reviewed in Schimmer & White 2010) and NUR77 (reviewed in Martin & Tremblay 2010).”
BackgroundYamauchi, S., Yamamoto, K., & Ogawa, K. (2022) · Biomedicines · doi:10.3390/biomedicines10020487 · Cited by 15
Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene
Mazaud‐Guittot, S., Bouchard, M. F., Robert, C., Robert, C., Goodyer, C. G., Silversides, D. W., & Viger, R. S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008454 · Cited by 14
“However, in more complex organs such as the gonads which are composed of different cell types that express GATA4 [6], this picture is less clear due to our inability to obtain a reliable in situ hybridization signal for the E1b-specific transcript.”
BackgroundSelf-citationSubculture of Germ Cell‐Derived Colonies with GATA4‐Positive Feeder Cells from Neonatal Pig Testes
Lee, K. H., Lee, W. Y., Kim, J., Park, C., Tae, J., Kim, J. H., Choi, Y., Kim, N. H., & Song, H. (2016) · Stem Cells International · doi:10.1155/2016/6029271 · Cited by 13
“GATA4 is known to be involved in the development and function of the mammalian testis [19].”
BackgroundBergeron, F., Sab, A. B., Bouchard, M., Taniguchi, H., Souchkova, O., Brousseau, C., Tremblay, J., Pilon, N., & Viger, R. S. (2019) · Andrology · doi:10.1111/andr.12601 · Cited by 13
“…of zinc finger DNA-binding proteins that are known for their many crucial roles, first in orchestrating critical developmental events, and later in promoting selective gene expression to allow different cell types to express their unique molecular signatures (Molkentin, 2000; Viger et al., 2008).”
BackgroundSelf-citationBelaguli, N. S., Zhang, M., Garcia, A.-H., & Berger, D. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035717 · Cited by 13
Mould, A. W., Duncan, R., Serewko-Auret, M. M., Loffler, K. A., Biondi, C., Gartside, M. G., Kay, G. F., & Hayward, N. K. (2008) · International Journal of Cancer · doi:10.1002/ijc.24057 · Cited by 13
McLean, Z. L., Appleby, S. J., Wei, J., Snell, R. G., & Oback, B. J. (2020) · Molecular Reproduction and Development · doi:10.1002/mrd.23443 · Cited by 13
A novel GATA 6 mutation in a child with congenital heart malformation and neonatal diabetes
Eifes, S., Chudasama, K., Molnes, J., Wagner, K., Hoang, T., Schierloh, U. H. E., Rocour-Brumioul, D., Johansson, S., Njølstad, P. R., & de Beaufort, C. E. (2013) · Clinical Case Reports · doi:10.1002/ccr3.33 · Cited by 12
“In vertebrates, this family of TFs is split into two subgroups encompassing in total six members including the hematopietic (GATA1/2/3) and cardiac groups (GATA4/5/6) [18].”
BackgroundLindholm, P., Soini, Y., Myllärniemi, M., Knuutila, S., Heikinheimo, M., Kinnula, V. L., & Salmenkivi, K. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.060533 · Cited by 12
Self-citationLaVoie, H. A., Kordus, R. J., Nguyen, J. B., Barth, J. L., & Hui, Y. Y. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.110.085969 · Cited by 10
“They are expressed in the adult endocrine tissues, including testes and ovaries [2, 3].”
BackgroundDeletion of the Prdm3 Gene Causes a Neuronal Differentiation Deficiency in P19 Cells
Leszczyński, P., Śmiech, M., Teeli, A. S., Haque, E., Viger, R. S., Ogawa, H., Pierzchała, M., & Taniguchi, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197192 · Cited by 11
“The structure of the DN construct is based on the GATA4 s quence, but due to the high conservation of the zinc finger domains within the GATA protein family, it can b used as a general competitor for GATA bindi [37].”
BackgroundSelf-citationYuan, X., Xia, L., Xia, D. O. N. G., Hu, S., Zhang, Y., Ding, F., Liu, H., Li, L., & Wang, J. (2014) · Journal of Reproduction and Development · doi:10.1262/jrd.2013-080 · Cited by 11
Vähätalo, R., Asikainen, T. M., Karikoski, R., Kinnula, V. L., White, C. W., Andersson, S., Heikinheimo, M., & Myllärniemi, M. (2010) · Neonatology · doi:10.1159/000317827 · Cited by 11
Self-citationThe GATA-Keepers of Ovarian Development and Folliculogenesis
LaVoie, H. A. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.122499 · Cited by 11
Parveen, S., Khan, M. F., Sultana, M., Rehman, S. U., & Shafique, L. (2024) · Journal of Applied Genetics · doi:10.1007/s13353-024-00924-6 · Cited by 10
“The DMRT gene family is likely to undergo a critical role in all of these sex-determination pathways and DMRT gene family characterization could pave valuable insights into the molecular mechanisms underlying sex determination and differentiation (Viger et al. 2008).”
ELT‐2 promotes O‐GlcNAc transferase OGT‐1 expression to modulate Caenorhabditis elegans lifespan
Su, L., Zhao, T., Li, H., Li, H., Su, X., Ba, X., Zhang, Y., Huang, B., Lü, J., & Li, X. (2020) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29817 · Cited by 11
“GATA4 was previously known to be a regulator of embryonic development.(22) Evidence shows that GATA4 triggers nuclear factor‐κB expression, resulting in activation of the senescence‐associated secretory phenotype (SASP) and promotion of cell senescence.”
BackgroundVerta, J., Barton, H. J., Pritchard, V. L., & Primmer, C. R. (2021) · Genome Biology and Evolution · doi:10.1093/gbe/evab059 · Cited by 8
Mehanovic, S., Pierre, K. J., Viger, R. S., & Tremblay, J. (2022) · Andrology · doi:10.1111/andr.13266 · Cited by 9
Self-citationDong, S., Xu, J., Meng, X., Jiang, X., Yang, D., Zhao, X., Li, X., & Ding, G. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.115108 · Cited by 9
Chakraborty, P., Anderson, R. L., & Roy, S. K. (2022) · Biology of Reproduction · doi:10.1093/biolre/ioac111 · Cited by 9
“Significant upregulation of Gata2 (expressed mostly in primordial oocytes) [45] and Gata4 (expressed in granulosa cells) [46] also occurred by E2.”
BackgroundPierre, K. J., & Tremblay, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113153 · Cited by 9
SUMO and ubiquitin modifications during steroid hormone synthesis and function
Talamillo, A., Martı́n, D., Hjerpe, R., Sánchez, J., & Barrio, R. (2010) · Biochemical Society Transactions · doi:10.1042/bst0380054 · Cited by 10
Testicular Steroidogenic Cells to the Rescue
Heikinheimo, M., Pihlajoki, M., Schrade, A., Kyrönlahti, A., & Wilson, D. B. (2015) · Endocrinology · doi:10.1210/en.2015-1222 · Cited by 9
Self-citationDistribution of Kaiso protein in mouse tissues
Shumskaya, V. S., Zhigalova, N., Prokhortchouk, A., & Prokhortchouk, E. (2014) · Histochemistry and Cell Biology · doi:10.1007/s00418-014-1261-7 · Cited by 9
“GATA-4 is expressed in Sertoli cells and is required for proper murine fetal testis development (Ketola et al. 2002; Viger et al. 2008).”
BackgroundGATA augments GNRH-mediated increases in Adcyap1 gene expression in pituitary gonadotrope cells
Thomas, R. L., Crawford, N., Grafer, C. M., Zheng, W., & Halvorson, L. M. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0089 · Cited by 9
“Although originally characterized in the hematopoietic and cardiac systems, GATA factors are now known to be expressed in hypothalamic GNRH neurons, the pituitary, the ovary, and the testes (LaVoie 2003, Viger et al. 2008).”
BackgroundGATA4 negatively regulates bone sialoprotein expression in osteoblasts
Song, I., Jeong, B., Choi, Y. J., Chung, Y., & Kim, N. (2016) · BMB Reports · doi:10.5483/bmbrep.2016.49.6.032 · Cited by 9
“hematopoietic stem cells, whereas GATA4, 5, and 6 are expressed in mesoderm- and endoderm-derived tissues (13, 14).”
BackgroundIskandarani, L., Romanelli, S., Hales, B. F., & Robaire, B. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae165 · Cited by 8
Khedr, M. H., Goma, A. A., Rashed, R. R., Tohamy, H. G., Shukry, M., & El-Kazaz, S. E. (2025) · Scientific Reports · doi:10.1038/s41598-025-07769-x · Cited by 8
“In contrast, GATA4 is pivotal for testicular development, regulating Sertoli and Leydig cell differentiation, testosterone synthesis through genes like STAR and CYP11A1, and germ cell survival 54 .”
Bouchard, M. F., Picard, J., Tremblay, J., & Viger, R. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231912009 · Cited by 8
“Over the last two decades, the importance of GATA factors for the development and functioning of the mammalian gonads has been demonstrated through the analysis of GATA loss-of-function models in mice as well as the in vitro characterization of the GATAdependence of the promoter regions of potential target genes (revi…”
BackgroundInfluentialSelf-citationMłynarczuk, J., Wrobel, M. H., Ziolkowska, A., & Kotwica, J. (2013) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2013.10.007 · Cited by 8
Lee, W.-Y., Lee, R., Song, H., Hur, T., Lee, S., Ahn, J., & Jhun, H. (2016) · Laboratory Animal Research · doi:10.5625/lar.2016.32.4.257 · Cited by 8
Sánchez-Lechuga, B., Saqlain, M., Ng, N., Colclough, K., Woods, C. P., & Byrne, M. M. (2020) · BMC Medical Genetics · doi:10.1186/s12881-020-01012-2 · Cited by 8
Bianchi, A., Lipchick, B. C., & Nikiforov, M. A. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6670-7_1 · Cited by 8
Genetic regulation of RNA splicing in human pancreatic isletsPreprint
Atla, G., Bonàs‐Guarch, S., Beucher, A., Cuenca-Ardura, M., García-Hurtado, J., Morán, I., Irimia, M., Prasad, R. B., Gloyn, A. L., Marselli, L., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.11.468254 · Cited by 8
Párraga-Leo, A., Sebastián-León, P., Devesa-Peiró, A., Marti-Garcia, D., Pellicer, N., Remohi, J., Sr., Domı́nguez, F., & Díaz-Gimeno, P. (2023) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-023-01131-4 · Cited by 7
“GATA6, the second prioritized TF that overlapped across the gene lists, is a transcription factor belonging to the GATA family, a highly conserved family of six zinc finger proteins [69].”
BackgroundBiology of childhood hepatoblastoma and the search for novel treatments
Pihlajoki, M., Eloranta, K., Nousiainen, R., Väyrynen, V., Soini, T., Kyrönlahti, A., Parkkila, S., Kanerva, J. A., Wilson, D. B., Pakarinen, M. P., et al. (2023) · Advances in Biological Regulation · doi:10.1016/j.jbior.2023.100997 · Cited by 7
Self-citationCao, H., Gao, H., Li, Z., Peng, G., Chen, Y., Jin, T., Zhu, C., Ji, H., & Dong, W. (2022) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2022.114066 · Cited by 7
Possible mechanism of GATA4 inhibiting myocardin activity during cardiac hypertrophy
Xu, Y., Liang, C., Luo, Y., Xing, W., & Zhang, T. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28178 · Cited by 7
“GATA4 is a zinc finger‐containing transcription factor that plays a central role in tissue‐specific gene expression in various tissues such as the heart.(9-12) In particular, GATA4 binding is required for the transcriptional activity of downstream target gene promoters.”
BackgroundLiao, S., Cheng, J., Zhao, W., Dai, C., Fu, Y., Li, B., Deng, Y., & Li, H. Z. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf031 · Cited by 6
Alterations in Gene Expression in Depression
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Ogawa, K., & Isaji, O. (2023) · Reproductive Biology · doi:10.1016/j.repbio.2023.100767 · Cited by 6
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Self-citation
Metadata
- Authors
- Viger, R. S., Guittot, S. M., Anttonen, M., Wilson, D. B., & Heikinheimo, M.
- Affiliations
- Centre hospitalier universitaire de Québec (CA)
- Ontogeny-Reproduction Research Unit (R.S.V., S.M.G.), CHUQ Research Centre, Quebec City, Canada G1V 4G2
- Department of Obstetrics and Gynecology and Women’s Health Research Program (M.A.), FI-00014 Helsinki, Finland
- St. Louis Children's Hospital (US)
- Corresponding author
- Viger, Robert S
- Heikinheimo, Markku
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-04-01
- Volume
- 22
- Issue
- 4
- Pages
- 781-798
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- PMC
- PMC2276466
- OpenAlex
- W2013216633
- Cited by
- 270
- References
- 235
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 12 · 2023: 10 · 2022: 15 · 2021: 21 · 2020: 12 · 2019: 15 · 2018: 12 · 2017: 11 · 2016: 19 · 2015: 21 · 2014: 24 · 2013: 13 · 2012: 16
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Helsingin Yliopisto
- Turun Yliopisto
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute of Diabetes and Digestive and Kidney Diseases (DK075618, R01DK075618)
- Institute of Gender and Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- GATA transcription factors, GATA-1, GATA2, GATA3, GATA4, GATA5, GATA6, endocrine development, endocrine function, gonads, pituitary gland, pancreas, adrenal gland, tissue-specific knockout mice
- MeSH terms
- Animals, Endocrine System Diseases, Endocrine System, Humans, Models, Biological, Transcription, Genetic, Protein Isoforms, GATA Transcription Factors
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